Radioactive specific irreversible or pseudo-irreversible binding reagents will be applied to cells and tissue specimens, with techniques for assuring specificity of reaction at chosen target macromolecules (e.g. an enzyme or receptor). Autoradiography in the light and electron microscopes will be used to locate these at the intra-cellular level. Grain and beta track counting methods will be used to give quantitative estimates of the enzyme or receptor molecules involved. The major application made will be mapping the molecular topography of cholinergic synapses, e.g. motor endplates. The numbers and types of cholinergic receptors, and of cholinesterases, at individual junctions will be further pursued, their spatial relations, and their relation to synaptic function. The method will also be used to monitor the selective extraction of these components. After purification by affinity chromatography and other separation techniques, the same approach will be used to follow the reassembly of these molecules in model membrane systems. An attempt will also be made to locate and isolate an ionophore macromolecule from the motor endplate, by parallel techniques.